Process for the preparation of vitamin K2
AssigneeKappa Bioscience AS
InventorsLars Skattebol, Inger Reidun Aukrust, Marcel Sandberg
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Abstract
Using a combination of Kumada, Suzuki and Biellmann chemistry, various menaquinones can synthesized rapidly and with stereochemical integrity offering a new way of preparing these vitamin K2 components for the pharmaceutical market. In one embodiment a process for the preparation of a compound of formula (I) is defined including a step in which (i) a compound of formula (II) is reacted formula (III) wherein R is an alkyl group; LG is a leaving group; m is an integer from 0 to 8; n is an integer from 0 to 9; and X is hydrogen, halide, hydroxyl or protected hydroxyl; in the presence of a copper, nickel or palladium catalyst.
Claims7
A process for the preparation of a compound of formula (I)
- comprising a step in which (i) a compound of formula (II) is reacted with a compound of formula (III)
- wherein R is an alkyl group;
- LG is a leaving group;
- m is an integer from 0 to 8;
- n is an integer of from 0 to 9;
- and
- X is hydrogen, halide, hydroxyl or protected hydroxyl;
- in the presence of a palladium catalyst;
- (ii) if necessary, converting X into a leaving group;
- (iii) reacting with a compound (V) or (VI)
- wherein Ar is aryl and m is independently as hereinbefore defined in the presence of a base;
- (iv) reducing the —SO2Ar or SAr group in the resulting compound to a hydride;
- and
- (v) converting the diprotected naphthoquinone into a naphthoquinone.
A process for the preparation of a compound of formula (I)
- comprising a step in which (i) a compound of formula (II) is reacted with a compound of formula (III)
- wherein R is an alkyl group;
- LG is a leaving group;
- m is an integer from 0 to 8;
- n is an integer of from 0 to 9;
- and
- X is hydrogen, halide, hydroxyl or protected hydroxyl;
- in the presence of a palladium catalyst;
- (ii) converting X into a SPh or —SO2Ph group to form compound (VII)
- wherein m is independently as hereinbefore defined;
- (iii) deprotonating (alpha to the sulphur) and reacting with a compound
- wherein m is independently as hereinbefore defined;
- (iv) reducing the phenylthioether or —SO2Ph to hydrogen;
- and
- (v) converting the diprotected naphthoquinone into a naphthoquinone ring.
A process for the preparation of a compound of formula (I)
- comprising a step in which (i) a compound of formula (II) is reacted with a compound of formula (III)
- wherein R is an alkyl group;
- LG is a leaving group;
- m is an integer from 0 to 8;
- n is an integer of from 0 to 9;
- and
- X is hydrogen, halide, hydroxyl or protected hydroxyl;
- in the presence of a palladium catalyst;
- (ii) if necessary converting X into a leaving group;
- (iii) reacting with a compound
- wherein m is independently as hereinbefore defined;
- in the presence of a Pd catalyst;
- and
- (iv) converting the diprotected naphthoquinone into a naphthoquinone.
Dependencies are inferred from the claim text.